Binding of outer surface protein A and human lymphocyte function-associated antigen 1 peptides to HLA-DR molecules associated with antibiotic treatment-resistant Lyme arthritis.

Abstract

OBJECTIVE:

To assess the binding of outer surface protein A (OspA) and human lymphocyte function-associated antigen 1 (hLFA-1) peptides to 5 major histocompatibility complex (MHC) molecules.

METHODS:

Peptide binding to the MHC molecules was determined by in vitro binding assays, and binding was correlated with the frequencies of the 5 MHC molecules in patients with treatment-resistant Lyme arthritis.

RESULTS:

The HLA-DRB1*0401 molecule bound both OspA(163-175) and hLFA-1alpha(L330-342) well. Although the magnitude of the binding was less, the DRB1*0404 molecule also showed binding of both peptides. The DRB1*0101 molecule bound OspA(163-175) well, but hLFA-1alpha(L330-342) only weakly; the DRB1*0801 or *1101 molecule bound both peptides weakly, if at all. The magnitude of OspA(163-175) binding correlated well with the frequencies of the DRB1 alleles in patients with treatment-resistant arthritis, but the binding of hLFA-1alpha(L330-342) showed only an association with the DRB*04 alleles.

CONCLUSION:

These correlations support the hypothesis that OspA(163-175) is the critical epitope in triggering antibiotic treatment-resistant Lyme arthritis. However, the inability of the DRB*0101 molecule to bind hLFA-1alpha(L330-342) suggests that this peptide may not be a relevant autoantigen, at least in DRB1*0101-positive patients.

• Authors: Allen C Steere, Ben Falk, Elise E Drouin, Lee Ann Baxter-Lowe, Juergen Hammer, Gerald T Nepom
• Journal: Arthritis and rheumatism (Arthritis Rheum) Vol. 48 Issue 2 Pg. 534-40 (Feb 2003) ISSN: 0004-3591 [Print] United States
• PMID: 12571864 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antigens, Surface
• Bacterial Outer Membrane Proteins
• Bacterial Vaccines
• HLA-DR Antigens
• Lipoproteins
• Lymphocyte Function-Associated Antigen-1
• OspA protein
• Peptide Fragments

Topics

• Antigens, Surface (metabolism)
• Bacterial Outer Membrane Proteins (metabolism)
• Bacterial Vaccines
• Binding, Competitive
• Drug Resistance, Bacterial
• Gene Frequency
• HLA-DR Antigens (genetics, metabolism)
• Humans
• In Vitro Techniques
• Lipoproteins
• Lyme Disease (drug therapy, genetics, immunology)
• Lymphocyte Function-Associated Antigen-1 (metabolism)
• Peptide Fragments (metabolism)